Researchers have discovered a new gene that stops cell division at the first sign of molecular mayhem. The research, published in the 27 July issue of Nature, reveals a new way in which cells orchestrate their division and could potentially help doctors select the right treatment for cancer patients.
Cells begin to reproduce by copying their genetic material, then split up in a process called mitosis. Diligent proteins known as checkpoints make sure that each step during mitosis proceeds only when prior steps are completed faithfully. Researchers suspect that problems with these checkpoints may lead to cancer, although they rarely find mutations in checkpoint genes in tumors. Until now, scientists knew only two types of checkpoints: those that work just before mitosis, and specialize in spotting DNA damage, and those acting during mitosis, which monitor a cellular scaffold made up of so-called microtubules. (The scaffold helps ensure that chromosomes are parceled evenly into the two new cells.)
In a hunt for new checkpoint players, Daniel Scolnick and Thanos Halazonetis of the Wistar Institute in Philadelphia discovered a new human gene named chfr, whose DNA sequence resembles that of other checkpoint genes. To find out how chfr works, they treated cancer cells with drugs that freeze the microtubule scaffold. Cells with defective chfr failed to recognize the problem immediately and got to the middle of mitosis, where they were finally stopped by a known checkpoint. But cells with chfr intact recognized the frozen scaffold immediately and stopped dividing at the very beginning of mitosis.
"It's cool," says cell biologist Conly Rieder of the Wadsworth Center in Albany, New York. "They've found the first checkpoint that monitors something other than DNA damage" at the onset of mitosis. "It's a whole new pathway that people weren't aware of, and now they have a molecular handle on it," adds molecular geneticist Stephen Elledge of the Baylor College of Medicine in Houston.
The finding may also have practical importance: Because cells that carry defective chfr are more sensitive to microtubule-disrupting drugs such as taxol, Halazonetis says that screening patients for this gene could help doctors in their selection of cancer-fighting agents.
Related sites
Halazonetis
Lab home page
The cell cycle and mitosis tutorial
Movies
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